Similar Datasets
Project description:Nitrosospira sp. 17 Nsp14 genome sequencing
| PRJNA322876 | ENA
Project description:SARS-CoV-2 virus mimics host mRNA by capping its viral RNA to promote replication and evade host immune sensing. SARS-CoV-2 NSP14 is the N7-guanosine methyltransferase (N7-MTase) responsible for RNA cap-0 formation. Targeting NSP14 for antiviral drug development is an under-explored but promising strategy. Here we conducted a high-throughput screening on natural products library derived from Chinese herbal medicine to discover Emodin as a SARS-CoV-2 NSP14 inhibitor. Exploring Emodin derivatives, Questin was identified with potent cellular inhibitory activity (EC50=249 nM) against SARS-CoV-2, which inhibits NSP14 in an RNA cap competitive manner, making it one the most potent anti-coronaviral natural products. Mechanistically, besides catalyzing viral RNA capping, NSP14 by itself could remodel host transcriptome such as enriching CREBBP, a key host factor in cellular cyclic AMP response pathway, to promote viral infection. As a result, targeting NSP14 by Questin significantly impairs viral Replication & Translation step and reverses host transcriptome remodeled by NSP14. We next validated Questin as a promising lead with significantly improved toxicity upon acute exposure in zebrafish larvae. Taken together, our study not only demonstrates Questin as a potent drug lead for clinical antiviral application, but also highlights multiple antiviral potentials of NSP14 as therapeutic target.
2024-12-31 | GSE282879 | GEO
Project description:We performed a transcriptomic analysis of H293T cells expressing individual SARS-CoV2 proteins. Overexpression of Nsp14, a protein known to be involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome, altering the expression of ≈4000 RNAs (3'RNAseq). These transcriptome changes strongly resemble the ones observed following SARS-CoV-2 infection. We performed a timecourse 3'RNA seq experiment and detected genes related to NFkB activation as deregulated soon after the transfection. We showed that the effect does not depend by the presence of the co-factor Nsp10 (total RNA seq) or by the exonuclease activity of Nsp14 (3' RNA seq of Nsp14 D90A/G92A and Nsp14D273 mutants). Finally we saw that the effect are mediated by the cellular enzyme IMPDH2, since treatment with MPA partially rescued the effect induced by Nsp14OE (3'RNA seq).
2022-03-11 | GSE179251 | GEO
Project description:Nitrosospira sp. Nsp44 Genome sequencing
| PRJNA370073 | ENA